Elucidation of the mechanism of insulin's stimulatory action on glucose metabolism and its perturbation in obesity and with altered dietary carbohydrate and fat content has been undertaken using the isolated rat adipose cell as a model. Mathematical modeling of the complex kinetics of insulin binding is in progress. Development of a 3H-cytochalasin B binding assay for quantitating the number of functional glucose transport systems in purified plasma membranes directly demonstrates that insulin's effect on transport occurs through an increase in the number of these sytems. Characterization of these transport systems and a detailed examination of the quantitative relationship between insulin binding and stimulation of transport are in progress. While insulin's primary effect occurs at the transport level, the adipose cell's lipolytic state appears to represent the primary regulator of the specific pathways for glucose carbon metabolism. The mechanisms controlling glucose carbon flux are under investigation. Obesity, as reflected in both the aging male Sprague Dawley rat and genetically obese Zucker Fatty rat, and altered dietary composition are accompanied by major alterations in the number of insulin-stimulatable glucose transport systems and the mechanisms regulating glucose carbon metabolism, but not in the mechanism of insulin action.